humoral and cellular immune response against sars-cov-2

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Humoral and cellular immune response against SARS-CoV-2 variants following heterologous and homologous Vaccination Reinhold Förster and Georg Behrens for the Hannover CoCo-Study group

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Humoral and cellular immune response against SARS-CoV-2 variants following heterologous and homologous

Vaccination

Reinhold Förster and Georg Behrensfor the Hannover CoCo-Study group

Analysis scheme

~ 4 month

~ 4 month

~ 4 month ~ 6 month

Parameters determined

• Anti-S1 IgG (Euroimmune; QuantiVac)• Anti-S- IgA• Surrogate virus neutralization test (sVNT)• S-specific B cells

• S-specific CD4 T cells• S-specific CD8 T cells• IGRA

No drop in ISW S-specific B cells

preliminary results

0.0

0.2

0.4

0.6

0.8

% I

SW

S

pik

e+

fro

m C

D19

+C

D2

0+

2 wks post boost

4 mth post boost

pre boost

** ****nsns

Strong drop in S1 antibodies 6 month after boostin BNT/BNT vaccinees

preliminary results

100

200

300

400

500

600

700

800A

nti-S

1 Ig

GR

U/m

l

0

ChAd ChAd ChAd ChAd

- ChAd -

ChAd

ChAd

ChAd

BNT BNT

2 wks 4 mths2 wks 4 mths

BNT BNT BNT

BNT BNT

2 wks 4 mths

BNT

BNT

6 mths

Median: 27.8 162.6 60.5 44.9 626.7 236.4 112.0 648.1 248.9 81.0

EuroImmune SARS-CoV-2 QuantiVac S1

1 RU = 3.2 BAU

-85% compared to 2 wks

Strong drop in S1 antibodies 6 month after boostin BNT/BNT vaccinees

preliminary results

100

200

300

400

500

600

700

800A

nti-S

1 Ig

GR

U/m

l

0

ChAd ChAd ChAd ChAd

- ChAd -

ChAd

ChAd

ChAd

BNT BNT

2 wks 4 mths2 wks 4 mths

BNT BNT BNT

BNT BNT

2 wks 4 mths

BNT

BNT

6 mths

Median: 27.8 162.6 60.5 44.9 626.7 236.4 112.0 648.1 248.9 81.0

EuroImmune SARS-CoV-2 QuantiVac S1

1 RU = 3.2 BAU

-85% compared to 2 wks

Hammerschmidt , re-submittedBosnjak et al, Cell. Mol Immunol; 2020

Surrogate virus neutralization test

Correlation of sVNT with pVNT

De Barros-Martins et al.; Nat. Med.; 2021

Alpha Beta Gamma Delta

Drop in neutralizing antibodies 4 month after boost

preliminary results

Strong drop in neutralizing antibodies 6 month after boostin BNT/BNT vaccinees

preliminary results

Frequencies of Spike-specific CD4+ T cells

preliminary results

Reduced frequencies of Spike-specific CD8+ T cells

preliminary results

Interferon gamma release assay

preliminary results

10

100

1000

10000

100000

IFN

-g m

UI/

ml

ChAd ChAd ChAd ChAd- ChAd -

ChAd

ChAdChAd

BNT BNT

2 wks 4 mths2 wks 4 mths

Summary

• Heterologous immunization with ChAd followed by BNT or MOD induces Spike –specificCD4 and CD8 T cell responses as well as high titers of neutralizing antibodies.

• 4 month after booster immunization a drop in T cell responses is observed with allimmunization protocols.

• ChAd/ChAd vaccinees have lowest Spike-specific T cell counts as well as lowest titers ofall vaccination proocols

• Mod/Mod induces highest titers of Delta neutralizing antibodies

• After six month Delta neutralizing antibodies dropped in BNT/BNT vaccinees byapprox 85%

Joana Barros-MartinsSwantje I. HammerschmidtIvan OdakChristiane RitterMichaela FriedrichsenChristian Schultze-Florey Inga RavensStefanie WillenzonAnja BubkeJasmin RistenpartAnika JanssenGünter BernhardtBerislav Bošnjak

Anne CossmannMetodi V. StankovGema Morillas Ramos Alexandra Dopfer-JablonkaAnnika HeidemannGeorg M. N. Behrens

George SsebyatikaThomas Krey

Markus Hoffmann Stefan Pöhlmann

Jan Münch

Christoph ThurmAnnegret ReinholdDirk Reinhold, Burkhart Schraven2

Acknowledgement

Inst. Immunologie, MHH Klinik für Rheumatologieund Immunology, MHH

Inst. für BiochemieUni Lübeck

Inst. für VirologieUni Ulm

Inst. für ImmunologieUni Magdeburg

Deutsches PrimatenZentrum, Göttingen